Ganglioside inhibition of glutamate-mediated protein kinase C translocation in primary cultures of cerebellar neurons.

AUTOR(ES)

Vaccarino, F

RESUMO

In primary cultures of cerebellar granule cells, protein kinase C (PKC) translocation and activation can be triggered by the stimulation of excitatory amino acid neurotransmitter receptors. Glutamate evokes a dose-related translocation of 4-beta-[3H]phorbol 12,13-dibutyrate ([3H]-P(BtO)2) binding sites from the cytosol to the neuronal membrane and stimulates the incorporation of 32P into a number of membrane proteins, particularly protein bands in the range of 80, 50, and 40 kDa. The glutamate-evoked PKC translocation is Mg2+ sensitive, is prevented by 2-amino-5-phosphonovalerate and phencyclidine, is not inhibited by nitrendipine (a voltage-dependent Ca2+-channel blocker) but is abolished by the removal of Ca2+ from the incubation medium, suggesting that glutamate-mediated Ca2+ influx is operative in the redistribution of PKC. Exposure of granule cells to the gangliosides trisialosylgangliotetraglycosylceramide (GT1b) or monosialosylgangliotetraglycosylceramide (GM1) inhibits the translocation and activation of PKC evoked by glutamate. These glycosphingolipids fail to interfere with glutamate binding to its high-affinity recognition site or with the [3H]P(BtO)2 binding, nor do they affect the Ca2+ influx. These gangliosides may prevent PKC translocation by interfering with the PKC binding to the neuronal membrane phosphatidylserine.

Documentos Relacionados

• Activation of protein kinase C promotes glutamate-mediated transmission at the neuromuscular junction of the mealworm.
• Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons
• Long-term activation of adenosine receptors regulates the survival and blocks glutamate-mediated neurotoxicity in cultures of retinal neurons
• Anomalous voltage dependence of channel blockade at a crustacean glutamate-mediated synapse.
• Sensitizing stimuli cause translocation of protein kinase C in Aplysia sensory neurons.